Project Summary Within a year of hip fracture 20-30% of patients die, and 50% percent lose the ability to walk. A consensus exists that infection with the human immunodeficiency virus (HIV) or the hepatis C virus (HCV) increases the likelihood of fracture risk. Co-infection with HIV and HCV is prevalent - - one third of infected HIV patients are also infected with HCV) - - thus the risk of hip fracture in this population is greatly pronounced. Evidence suggests that current standard modalities used to measure bone strength, dual energy X-ray absorptiometry (DXA) and the Fracture Risk Assessment Tool (FRAX), underestimate this risk in HIV+/HCV+ patients. To address this issue, we will apply novel magnetic resonance imaging (MRI) methods to the proximal femur (i.e., hip) in three patient cohorts available through a recently funded NIH project in order to determine how MRI analyzes bone deficits inaccessible by BMD/FRAX scores, how the methodology may provide clinical tools useful for future HIV+/HCV+ trials, and how direct-acting antiviral (DAA) treatment of HCV affects bone strength in light of possible future treatment innovations for fracture risk in HIV+/HCV+ and HCV+ patients. In this work, the investigators propose to test and compare bone strength, trabecular microstructure, cortical porosity, and marrow fat using MRI of the proximal femur in HIV+/HCV+ patients, in HCV+ patients, and in unaffected individuals. HIV+/HCV+ coinfection is predicted to decrease bone strength, present abnormal trabecular structure, increase cortical porosity, and present abnormal marrow fat fraction, in comparison to the HCV+ and uninfected cohorts. Group differences are predicted to be less pronounced in BMD as assessed by DXA and FRAX scores. Identical parameters will be tested for each of the three cohorts 18 months after initiation of a 12-week treatment of DAA therapy in HIV+/HCV+ and HCV+ individuals. Treating HIV with antiretroviral therapy (ART) is known to have immediate negative effects on overall bone strength, but less information exists about bone deficit changes following HCV cure with DAA treatment. Cure of HCV is predicted to result in increased bone strength, improved trabecular microstructure, decreased cortical porosity, and improved marrow fat fraction in the HCV+ and HIV+/HCV+ cohorts, but again predicted to be less pronounced as assessed by DXA and FRAX scores. The HCV+ cohort is predicted to have larger positive changes concerning these parameters in comparison to the HIV+/HCV+ group. The proposed project has the potential to change and improve how bone disease is clinically managed and to reduce the burdens of hip fractures in patients infected with HIV and HCV.